Several publications and patent documents are cited throughout the specification in order to describe the state of the art to which this invention pertains. Each of these citations is incorporated herein by reference as though set forth in full.
There is an extraordinary need for new and better neurotoxicity assays, particularly developmental neurotoxicity (DNT) assays, that can be carried out with higher speed and lower cost (Bal-Price et al. (2008) Neurotoxicol., 29:520-531). Otherwise, the important goal of testing tens of thousands of drugs and chemicals already in the environment will never be achieved (Landrigan, P. (2010). Curr. Opin. Pediatr., 22:219-225). The concern about having so many untested compounds in the environment is not just a philosophical one. Rather, there is increasing evidence that environmental factors which have changed in recent decades are responsible for some large part of the increasing rates of autism spectrum disorders (Hertz-Picciotto & Delwiche (2009) Epidemiology 20:84-90). Beyond this concern, better methods are needed for testing compounds in the drug-development pipeline for potential neurotoxicity prior to marketing. In addition, there is a compelling rationale to reduce the reliance on whole-animal testing in mammals (Flecknell, P. (2002) ALTEX 19:73-78). In particular, there is a need to greatly reduce the use of rats for neurotoxicity testing because those methods are so expensive and slow that they, in effect, serve as an obstacle to conducting neurotoxicity testing. Furthermore, neurotoxicity testing in rats does not allow for evaluation of genetic influences on sensitivity to neurotoxic compounds. The instant invention solves the above problems.